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Advances in molecular therapies in patients with brain tumors
Ivo W Tremont-Lukats1, Mark R Gilbert
1Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Background:
We are witnessing the development of new treatment modalities for primary brain tumors. An area under intense investigation is the use of small molecules targeting intracellular signaling pathways that interfere with growth, invasion, and metastasis of high-grade gliomas.
Methods:
We review clinical trials of small molecules in adults with brain tumors. This search included electronic databases, specialty journals, textbooks, proceedings, and Web sites of the National Cancer Institute and other cooperative brain tumor groups in Europe and the United States.
Results:
Several drugs with the ability to down-regulate the growth and invasion of malignant gliomas are at various stages of testing. Most of these focus on interfering with oncogenic and tumor survival pathways. Examples include inhibitors of tyrosine kinases, farnesyltransferases, and matrix metalloproteinases. These molecules are at different stages of testing, and a conclusive picture of which drug is most effective, either alone or in combination, needs better definition. The metalloproteinase inhibitor marimastat with temozolomide has given the best results to date in phase II trials, increasing the rate of 6-month progression-free survival for recurrent glioblastoma multiforme and anaplastic gliomas.
Conclusions:
As our understanding of the biology of gliomas increases and new drugs targeting specific molecular pathways enter well-designed cooperative trials, the control and prognosis of these tumors should improve.
Insights
New small molecule drugs targeting brain tumor pathways show promise. Marimastat combined with temozolomide improved progression-free survival in phase II trials for high-grade gliomas.
Area of Science:
- Neuro-oncology
- Molecular targeted therapy
- Cancer drug development
Background:
- Primary brain tumors, particularly high-grade gliomas, necessitate novel therapeutic strategies.
- Intracellular signaling pathways are key targets for inhibiting glioma growth, invasion, and metastasis.
- Small molecule inhibitors represent a promising area of investigation for brain tumor treatment.
Purpose of the Study:
- To review clinical trials of small molecules in adult brain tumor patients.
- To identify emerging targeted therapies for malignant gliomas.
Main Methods:
- Comprehensive literature search of clinical trials involving small molecules for brain tumors.
- Inclusion of data from electronic databases, journals, textbooks, and cooperative brain tumor group websites.
- Focus on studies investigating targeted intracellular signaling pathways.
Main Results:
- Multiple small molecule drugs targeting oncogenic and tumor survival pathways are in development.
- Inhibitors of tyrosine kinases, farnesyltransferases, and matrix metalloproteinases are among the agents tested.
- The combination of marimastat (a metalloproteinase inhibitor) and temozolomide demonstrated improved 6-month progression-free survival in phase II trials for recurrent glioblastoma multiforme and anaplastic gliomas.
Conclusions:
- Advancements in understanding glioma biology are driving the development of targeted drugs.
- Well-designed clinical trials are crucial for evaluating the efficacy of these novel therapies.
- Improved control and prognosis for glioma patients are anticipated with the integration of targeted molecular therapies.